Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN929M8)

• DOT Name: Lysosome membrane protein 2 (SCARB2)
• Synonyms: 85 kDa lysosomal membrane sialoglycoprotein; LGP85; CD36 antigen-like 2; Lysosome membrane protein II; LIMP II; Scavenger receptor class B member 2; CD antigen CD36
• Gene Name: SCARB2
• Related Disease:
  Progressive myoclonus epilepsy
  Action myoclonus-renal failure syndrome
  Astrocytoma
  Cardiac failure
  Charcot marie tooth disease
  Childhood epilepsy with centrotemporal spikes
  Congestive heart failure
  Dilated cardiomyopathy
  Gaucher disease
  Glomerulosclerosis
  Hyperprolactinaemia
  Neoplasm
  Parkinson disease
  Polyneuropathy
  Gaucher disease type I
  Nephropathy
  Obesity
  Unverricht-Lundborg syndrome
  Adult neuronal ceroid lipofuscinosis
  Alzheimer disease
  Asthma
  Demyelinating polyneuropathy
  Enterovirus infection
  Epilepsy
  Fabry disease
  Hand, foot and mouth disease
  Lewy body dementia
  Nephrotic syndrome
  Prostate cancer
  Prostate carcinoma
• UniProt ID: SCRB2_HUMAN
• PDB ID: 4F7B; 4Q4B; 4Q4F; 4TVZ; 4TW0; 4TW2; 5UPH; 5XBM; 6I2K
• Pfam ID: PF01130
• Sequence:
  MGRCCFYTAGTLSLLLLVTSVTLLVARVFQKAVDQSIEKKIVLRNGTEAFDSWEKPPLPV
  YTQFYFFNVTNPEEILRGETPRVEEVGPYTYRELRNKANIQFGDNGTTISAVSNKAYVFE
  RDQSVGDPKIDLIRTLNIPVLTVIEWSQVHFLREIIEAMLKAYQQKLFVTHTVDELLWGY
  KDEILSLIHVFRPDISPYFGLFYEKNGTNDGDYVFLTGEDSYLNFTKIVEWNGKTSLDWW
  ITDKCNMINGTDGDSFHPLITKDEVLYVFPSDFCRSVYITFSDYESVQGLPAFRYKVPAE
  ILANTSDNAGFCIPEGNCLGSGVLNVSICKNGAPIIMSFPHFYQADERFVSAIEGMHPNQ
  EDHETFVDINPLTGIILKAAKRFQINIYVKKLDDFVETGDIRTMVFPVMYLNESVHIDKE
  TASRLKSMINTTLIITNIPYIIMALGVFFGLVFTWLACKGQGSMDEGTADERAPLIRT
• Function: Acts as a lysosomal receptor for glucosylceramidase (GBA1) targeting; (Microbial infection) Acts as a receptor for enterovirus 71.
• KEGG Pathway: Lysosome (hsa04142)
• Reactome Pathway:
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Progressive myoclonus epilepsy	DISAMCNS	Definitive	Autosomal recessive	[1]
Action myoclonus-renal failure syndrome	DISI2BZN	Strong	Autosomal recessive	[2]
Astrocytoma	DISL3V18	Strong	Biomarker	[3]
Cardiac failure	DISDC067	Strong	Biomarker	[4]
Charcot marie tooth disease	DIS3BT2L	Strong	Genetic Variation	[5]
Childhood epilepsy with centrotemporal spikes	DISKT2L5	Strong	CausalMutation	[6]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[4]
Dilated cardiomyopathy	DISX608J	Strong	Genetic Variation	[7]
Gaucher disease	DISTW5JG	Strong	Biomarker	[8]
Glomerulosclerosis	DISJF20Z	Strong	Biomarker	[2]
Hyperprolactinaemia	DISLIZS4	Strong	Genetic Variation	[9]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[10]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[11]
Polyneuropathy	DISB9G3W	Strong	Genetic Variation	[7]
Gaucher disease type I	DIS87KKY	moderate	GermlineModifyingMutation	[12]
Nephropathy	DISXWP4P	moderate	Genetic Variation	[13]
Obesity	DIS47Y1K	moderate	Altered Expression	[14]
Unverricht-Lundborg syndrome	DISG4WLX	Supportive	Autosomal recessive	[15]
Adult neuronal ceroid lipofuscinosis	DIS5UHAA	Limited	Biomarker	[16]
Alzheimer disease	DISF8S70	Limited	Altered Expression	[17]
Asthma	DISW9QNS	Limited	Biomarker	[18]
Demyelinating polyneuropathy	DIS7IO4W	Limited	Biomarker	[7]
Enterovirus infection	DISH2UDP	Limited	Altered Expression	[19]
Epilepsy	DISBB28L	Limited	Biomarker	[7]
Fabry disease	DISUUQJF	Limited	Biomarker	[20]
Hand, foot and mouth disease	DISKJHLL	Limited	Biomarker	[19]
Lewy body dementia	DISAE66J	Limited	Altered Expression	[17]
Nephrotic syndrome	DISSPSC2	Limited	Genetic Variation	[21]
Prostate cancer	DISF190Y	Limited	Altered Expression	[22]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[22]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Lysosome membrane protein 2 (SCARB2).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Lysosome membrane protein 2 (SCARB2).	[33]

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lysosome membrane protein 2 (SCARB2).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Lysosome membrane protein 2 (SCARB2).	[25]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Lysosome membrane protein 2 (SCARB2).	[26]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Lysosome membrane protein 2 (SCARB2).	[27]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Lysosome membrane protein 2 (SCARB2).	[28]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Lysosome membrane protein 2 (SCARB2).	[29]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Lysosome membrane protein 2 (SCARB2).	[30]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Lysosome membrane protein 2 (SCARB2).	[31]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Lysosome membrane protein 2 (SCARB2).	[32]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Lysosome membrane protein 2 (SCARB2).	[34]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Lysosome membrane protein 2 (SCARB2).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Lysosome membrane protein 2 (SCARB2).	[36]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of Lysosome membrane protein 2 (SCARB2).	[37]

References

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• [20] A Human Stem Cell Model of Fabry Disease Implicates LIMP-2 Accumulation in Cardiomyocyte Pathology.Stem Cell Reports. 2019 Aug 13;13(2):380-393. doi: 10.1016/j.stemcr.2019.07.004. Epub 2019 Aug 1.
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